Modern anesthetic drugs have revolutionized medical care, and their use is increasing as the population ages1. Each year, more than 234 million surgical procedures necessitating general anesthesia are performed worldwide, yet surprisingly little is known about how these drugs work. Anesthetics cause a constellation of behavioural effects, including sedation, immobility, and memory blockade, which together allow the patient to tolerate the surgical trauma2. Memory blockade is an essential component of the anesthetic state.
Most patients, and even most physicians, assume that cognitive function rapidly returns to its normal preoperative state once an anesthetic has been metabolized15, 16. Unfortunately, many patients who undergo major surgery experience a marked deterioration in cognitive performance after the operation, a condition known as postoperative cognitive dysfunction (POCD)2-6, 17. For reasons that are not understood, many patients experience postoperative memory deficits that persist long after the anesthetic has been metabolize2-6. Large clinical trials have shown that cognitive dysfunction is present in over 25% of patients at the time of discharge and in 10% at 3 months after surgery3.
Both the anesthetic and the surgery contribute to postoperative memory deficits. We and others have shown that anesthesia without surgery impairs learning, even days after administering the anesthetic7, 25. Similarly, surgery alone, performed under local or regional anesthesia, causes persistent memory deficits in human patients and laboratory animals3, 19. Clinical and animal studies have indicated that the most vulnerable cognitive domains, explicit memory and spatial memory, are dependent on the hippocampus20-24.
The cause of postoperative/pos-anesthetic memory impairment is unknown, and the expected risk factors, such as hypoxia and low blood pressure, do not correlate with the condition7. Post-anesthetic memory deficits represent an undesirable and poorly understood adverse effect. Such mental deficits after anesthetic/surgery are associated with a reduction in quality of life, premature retirement, an increase in the rate of admission to long-term care facilities, and premature death18, 19. Most importantly, there are no known treatments or prevention strategies.
Therefore, a need exists to provide prevention and/or treatment for memory impairment caused by anesthesia, surgery and/or inflammation.